Elution Protocols and Dosages for Radiopharmaceutical Elution System

ABSTRACT

A radioisotope elution system is provided. The radioisotope elution system may comprise a controller that is configured to calculate the available amount of daughter radioisotope at any time during establishment of the equilibrium for decay of the parent radioisotope into its daughter radioisotope. The radioisotope elution system may comprise a controller that is configured to schedule various patient infusions planned for the next following days and weeks in accordance with the available amount of daughter radioisotope on each day. The elution system may also comprise a controller that is connected to the imaging software of a radioisotope imaging device, where the radioisotope imaging device is arranged for imaging the patient or a region of the patient; and the controller is configured to start an image acquisition at a predetermined time.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims the benefit of priority to U.S.Provisional Application Ser. No. 62/826,711, filed Mar. 29, 2019, theentire contents of which are incorporated herein by reference and is acontinuation of application Ser. No. 16/832,436, filed Mar. 27, 2020.

TECHNICAL FIELD

The present invention relates in general to nuclear medicine and, inparticular, to radiopharmaceutical medical devices for the generation ofa radiopharmaceutical composition for treating and/or diagnosing adisease or a condition.

BACKGROUND

Radioisotopes play a pivotal role in diagnosis and mitigation of variousdiseased conditions. For example, ⁶⁰Co in treatment of cancer, ¹³¹I intreatment of hyperthyroidism, ¹⁴C in breath tests, ^(99m)Tc and ⁸²Rb astracers in myocardial perfusion imaging. The radioisotopes forpharmaceutical use are produced either by nuclear bombardment incyclotron in specially approved remote sites or in-situ by employingradioisotope generators at the site of use.

Rubidium (⁸²Rb) is used as a positron emission tomography (PET) tracerfor non-invasive measurement of myocardial perfusion. Rubidium-82 isproduced in situ by radioactive decay of strontium-82. Rubidium elutionsystems utilize doses of rubidium-82 generated by elution within aradioisotope generator, and infuse the radioactive solution into apatient. The infused dose of radiopharmaceutical is absorbed by cells ofa target organ of the patient and emit radiation which is detected by aPET scanner in order to generate an image of the organ.

There is a need to improve the dosage of infused pharmaceutical, andincrease the number of patients that can be diagnosed/treated per daywith minimal waiting time and radiation exposure.

SUMMARY

The present invention aims to provide elution systems that maximize theusage of parent radioisotope and minimize the recharge time between twosuccessive elutions.

The present invention also aims to provide the minimal and adequate doseof radiopharmaceutical to a patient.

It is an object of the present invention to determine the minimalregeneration time between two successive elutions of specific doses.

It is also an object of the present invention to maximize the usage ofparent isotope present in the generator system.

It is another object of the present invention to minimize the radiationexposure to the patients.

It is yet another object of the present invention to minimize thewaiting time between elutions. The present invention concerns any of thefollowing items:

-   -   1. A radioisotope elution system comprising a radioisotope        generator containing a parent radioisotope that decays into a        daughter radioisotope, a patient line for infusing a patient        with a daughter radioisotope eluate generated by the generator,        a pump for pumping an eluant from an eluant reservoir into the        generator, a controller for controlling the pump; wherein the        system is characterized in that:    -   the controller is configured to calculate a real time amount of        daughter radioisotope that is available in the generator during        the establishment of an equilibrium for decay of the parent        radioisotope into its daughter radioisotope; and    -   the controller provides real time information during        establishment of the equilibrium, said information comprising        the available amount of daughter radioisotope that can be        infused to the patient.    -   2. The radioisotope elution system of item 1, wherein the real        time information further comprises the flow rate of infusion        that is requested to infuse said available amount, and/or the        duration of infusion that is requested to infuse said available        amount.    -   3. The radioisotope elution system of item 1 or 2, wherein the        system further comprises a user interface, and wherein the        controller displays the real time information on the interface.    -   4. The radioisotope elution system of item 3, wherein the        available amount of daughter radioisotope is displayed in terms        of activity dose unit.    -   5. The radioisotope elution system of any one of items 1 to 4,        wherein the controller is further configured to calculate the        time lapsed until the establishment of an equilibrium for decay        of the parent radioisotope into its daughter radioisotope.    -   6. The radioisotope elution system of item 5, wherein the        controller provides the information about the time lapsed until        the establishment of the equilibrium.    -   7. The radioisotope elution system of any one of items 1 to 6,        wherein the controller notifies a user of the system immediately        once the available amount of daughter radioisotope reaches a        needed amount that the user has entered into the system.    -   8. The radioisotope elution system of item 7, wherein the        notification is audible or visual, or both.    -   9. The radioisotope elution system of any one of items 1 to 8,        wherein the daughter radioisotope is rubidium-82.    -   10. The radioisotope elution system of any one of items 1 to 9,        wherein a following patient infusion is pre-programmed and        wherein the controller starts a patient infusion corresponding        to said pre-programmed patient infusion automatically when the        available amount of daughter radioisotope in the generator has        reached a sufficient amount for infusing the following        pre-programmed patient infusion.    -   11. The radioisotope elution system of any one of items 1 to 10,        wherein the system further comprises:    -   a generator line by which the eluate exits the generator;    -   a tubing line system that directs the eluant from the eluant        reservoir to the generator, wherein the tubing line system        comprises a first valve that directs alternatively the eluant to        the generator or a bypass line, wherein the bypass line is        merged with a generator line at a merging point;    -   wherein the system further comprises a radioactivity detector        downstream the merging point for detecting the radioactivity of        a mixture of an eluate generated by the generator and the eluant        directed by the bypass line;    -   wherein the controller controls the first valve and the pump for        adjusting:    -   i) the radioactivity per volume at the merging point, or    -   ii) a flow rate of the mixture at the merging point, or    -   iii) both.    -   12. The radioisotope elution system of item 11, wherein the        radioactivity per volume or the flow rate is determined in        accordance with the patient requirement.    -   13. The radioisotope elution system of item 12, wherein the        patient requirement is based on at least one characteristic of        the patient, said at least one characteristic of the patient is        age, sex, body weight, body mass index, body circumference        and/or a surface area.    -   14. The radioisotope elution system of item 12, wherein the        patient requirement is based on the organ or the part of the        patient that is intended for imaging.    -   15. The radioisotope elution system of item 14, wherein the        organ or the part of the patient is heart, brain, kidney, limb        or blood vessel; and wherein the daughter radioisotope is        rubidium-82.    -   16. The radioisotope elution system of any one of items 1 to 15,        wherein the system further comprises a radioisotope imaging        device for imaging the patient or an organ or a part of the        patient; wherein the controller is connected to an imaging        software of the radioisotope imaging device.    -   17. The radioisotope elution system of item 16, wherein the        controller is configured to start an image acquisition at a        predetermined time after the patient infusion has begun or has        ended.    -   18. The radioisotope elution system of any one of items 1 to 17,        wherein the system further comprises a tubing system        interconnecting the radioisotope elution system with a stress        agent reservoir, wherein the controller is configured to control        the infusion of a stress agent contained in the stress agent        reservoir to the patient.    -   19. The radioisotope elution system of item 18, wherein the        stress agent infusion is performed at a predetermined time prior        to infusing the daughter radioisotope eluate to the patient.    -   20. The radioisotope elution system of item 18 or 19, wherein        the stress agent infusion is automated and the controller        controls the dose of stress agent and the pre-determined time        prior to infusing a patient with a daughter radioisotope eluate.    -   21. The radioisotope elution system of item 20, wherein the dose        of stress agent is determined in accordance with the patient        requirement.    -   22. A radioisotope elution system comprising a radioisotope        generator containing a parent radioisotope that decays into a        daughter radioisotope, a patient line for infusing a patient        with a daughter radioisotope eluate generated by the generator,        a pump for pumping an eluant from an eluant reservoir into the        generator, a controller for controlling the pump, and a user        interface; wherein the system is characterized in that:    -   the controller is configured to calculate an amount of daughter        radioisotope that is available in the generator for a patient        infusion and estimate the amount of daughter radioisotope that        will be available in the generator the following days;    -   the controller is configured to receive information from the        user about the patient infusions that are intended; and    -   the controller is configured to display on the interface a        recommended day for infusing each of the patient infusions that        are intended.    -   23. A radioisotope elution system comprising a radioisotope        generator containing a parent radioisotope that decays into a        daughter radioisotope, a patient line for infusing a patient        with a daughter radioisotope eluate generated by the generator,        a pump for pumping an eluant from an eluant reservoir into the        generator, and a controller for controlling the pump; wherein        the system is characterized in that:    -   the system further comprises a radioisotope imaging device for        imaging the patient or an organ or a part of the patient; and    -   the controller is connected to an imaging software of the        radioisotope imaging device.    -   24. The radioisotope elution system of item 23, wherein the        controller is configured to start an image acquisition at a        predetermined time after the patient infusion has begun or has        ended.    -   25. The radioisotope elution system of item 23 or 24, wherein        the system further comprises a tubing system interconnecting the        radioisotope elution system with a stress agent reservoir,        wherein the controller is configured to control the infusion of        a stress agent contained in the stress agent reservoir to the        patient.    -   26. The radioisotope elution system of item 25, wherein the        stress agent infusion is performed at a predetermined time prior        the daughter radioisotope eluate infusion.    -   27. The radioisotope elution system of item 25 or 26, wherein        the stress agent infusion is automated and the controller        controls the dose of stress agent and the pre-determined time        prior to infusing a patient with a daughter radioisotope eluate.    -   28. The radioisotope elution system of item 27, wherein the dose        of stress agent is determined in accordance with the patient        requirement.    -   29. The radioisotope elution system of item 28, wherein the        patient requirement is based on at least one characteristic of        the patient, said at least one characteristic of the patient is        age, sex, body weight, body mass index, body circumference        and/or a surface area.    -   30. The radioisotope elution system of item 28, wherein the        patient requirement is based on the organ or the part of the        patient that is intended for imaging.    -   31. The radioisotope elution system of item 30, wherein the        organ or the part of the patient is heart, brain, kidney, limb        or blood vessel; and wherein the daughter radioisotope is        rubidium-82.

BRIEF SUMMARY OF DRAWINGS

Further features and advantages of the present invention will becomeapparent from the following detailed description, taken in combinationwith the appended drawings, in which:

FIG. 1 is a block diagram schematically illustrating principal elementsof a Rubidium elution system in accordance with an embodiment of thepresent invention; and

FIG. 2 is a block diagram schematically illustrating principal elementsof a Rubidium elution system in accordance with another embodiment ofthe present invention.

It will be noted that throughout the appended drawings, like featuresare identified by like reference numerals.

DETAILED DESCRIPTION

The present invention can be more readily understood by reading thefollowing detailed description of the invention and includedembodiments.

As used herein, the term “column” refers to the functional component ofa radiopharmaceutical generator, wherein a hollow column made up of aradiation resistant material is packed with an ion exchange resin,wherein the ion exchange resin is loaded or charged with parentradioisotope. The ion exchange resin has higher affinity for parentradioisotope as compared to daughter radioisotope. Thus, on elution witha suitable medium, daughter radioisotope gets eluted from the generatorwhile parent radioisotope stays adsorbed to matrix of ion exchangeresin.

The daughter radioisotope is formed in-situ by radioactive decay ofparent radioisotope in the column.

As used herein, the term “generator system” or “generator” or“radioisotope generator” refers to one or more columns containingradioisotope in a shielded container wherein a radiation shieldingmaterial surrounds the columns in order to absorb the energy radiatingfrom the generator container, thus protecting the end user from gettingexposed to harmful radiation. The radioisotopes which can be used withradioisotope generator include, but are not limited to ⁹⁹Mo/^(99m)Tc,⁹⁰Sr/⁹⁰Y, ⁸²Sr/⁸²Rb, ¹⁸⁸W/¹⁸⁸Re, ⁶⁸Ge/⁶⁸Ga, ⁴²Ar/⁴²K, ⁴⁴Ti/⁴⁴Sc,⁵²Fe/^(52m)Mn, ⁷²Se/⁷²As, ⁸³Rb/^(83m)Kr; ¹⁰³Pd/^(103m)Rh,¹⁰⁹Cd/^(109m)Ag, ¹¹³Sn/^(113m)In, ¹¹⁸Te/¹¹⁸Sb, ¹³²Te/¹³²I,¹³⁷Cs/^(137m)Ba, ¹⁴⁰Ba/¹⁴⁰La, ¹³⁴Ce/¹³⁴La, ¹⁴⁴Ce/¹⁴⁴Pr, ¹⁴⁰Nd/¹⁴⁰Pr,¹⁶⁶Dy/¹⁶⁶Ho, ¹⁶⁷Tm/^(167m)Er, ¹⁷²Hf/¹⁷²Lu, ¹⁷⁸W/¹⁷⁸Ta, ¹⁹¹Os/^(191m)Ir,¹⁹⁴Os/¹⁹⁴Ir, ²²⁶Ra/²²²Rn and ²²⁵Ac/²¹³Bi.

As used herein, the term “radioisotope regeneration time” or“regeneration time” or “idle time” or “recharge time” refers to the timerequired for generator system to establish an equilibrium between rateof production of daughter radioisotope and rate of decay of daughterradioisotope. Once the radioisotope has been eluted out from the column,the generator cannot be used again instantly. The generator needs sometime for formation of daughter radioisotope by radioactive decay ofparent radioisotope and for establishment of equilibrium between rate ofproduction of daughter radioisotope and rate of decay of daughterradioisotope.

As used herein, the terms “medical unit” or “radioisotope medical unit”,or “radioisotope medical device” or “radioisotope elution device” areused interchangeably. In an embodiment, it refers to elution systemcontained in cabinet structures. Optionally, the medical unit can becarried by a mobile cart.

As used herein, the term “elution system” refers to infusion systemmeant for generating a solution containing radioisotopes, measuring theradioactivity in the solution, and infusing the solution into a patient.

As used herein, the term “Sr/Rb elution system” or “⁸²Sr/⁸²Rb elutionsystem” refers to infusion system meant for generating a solutioncontaining ⁸²Rb, measuring the radioactivity in the solution, andinfusing the solution into a patient in order to perform various studieson the patient's heart.

As used herein, the term “shielded components” refers to components thatare shielded by a radiopaque material. The “shielded components” mayinclude, for instance, a generator, a dose calibrator, an activitydetector and/or a waste container. The terms “waste reservoir” and“waste container” are interchangeably used herein.

As used herein, the term “shielded” refers to the condition of beinghoused within a compartment that provides a barrier to radioactiveradiation generated by the radioisotope. The shielding preventsradiation hazard and exposure of an operator or user to unwantedradiation. Said shielding may be made up of any radiation attenuatingmaterial including but not limited to depleted uranium (U), lead (Pb),tin (Sn), antimony (Sb), tungsten (W), bismuth (Bi) or any othersuitable element or material and any combination thereof.

As used herein, the term “non-shielded components” refers to pumpsystem, valve system, saline reservoir, computer system and/orcontroller.

As used herein, the term “eluant” refers to the liquid or the fluid usedfor selectively leaching out the daughter radioisotopes from thegenerator column.

As used herein, the term “eluate” refers to the radioactive eluant afteracquisition of daughter radioisotope from the generator column.

In an embodiment, the present invention concerns a radiopharmaceuticalelution system comprising a suitable eluant contained in an eluantreservoir, a radioactive generator containing a parent radioisotope thatdecays into a corresponding daughter radioisotope, a first tubing lineinterconnecting the eluant reservoir and the generator, a pump forpumping the eluant from the eluant reservoir through said first tubingline, a first valve located on said tubing line and downstream the pumpfor directing the eluant to the generator or to a by-pass line, aneluate exiting the generator through a second tubing line and containingthe daughter radioisotope, the second tubing line having a connection toreceive the eluant from the by-pass line, a radioactivity detector onthe second tubing line downstream said connection, a second valve on thesecond tubing line downstream the detector for directing the eluate to apatient line or to a waste line that is connected to a waste reservoir,the patient line is adapted for infusion into a patient, a controllerfor controlling the pump, the first valve and the second valve, and forreceiving the information from the detector.

In an embodiment, the radiopharmaceutical elution system is a rubidium(⁸²Rb) elution system, which comprises the components described in FIG.1 . In an embodiment, the elution system comprises reservoir 4 ofsterile saline solution (e.g. 0.9% Sodium Chloride Injection); a pump 6for drawing saline from the reservoir 4 through the supply line 5 andthe generator line (between 30 and 22) at a desired flow rate; agenerator valve 16 for proportioning the saline flow between astrontium-rubidium (⁸²Sr/⁸²82Rb) generator 8 and a bypass line 18 whichcircumvents the generator 8; a positron detector 20 located downstreamof the merge point 22 at which the generator and bypass flows merge andfrom which fluid flow travels via fluid line 33 to the positron detector20; and a patient valve 24 for controlling supply of active saline to apatient outlet 10 via patient line 40 and to a waste reservoir 26. Acontroller 28 in communication with a user interface computer 44 ispreferably connected to the pump 6, positron detector 20 and valves 16and 24 to control the elution system 14 in accordance with a desiredcontrol algorithm.

FIG. 2 is a block diagram schematically illustrating principal elementsof a Rubidium elution system in accordance with another embodiment ofthe present invention. The Rubidium elution system of FIG. 2 has similarelements as the Rubidium elution system of FIG. 1 , and additionalelements. These additional elements preferably include one or more of aprinter 50 and USB (Universal Serial Bus; or other communications port)port 52, a pressure detector 62, an eluate line 41, a dose calibrator56, a flow regulator 66, or a UPS (Uninterruptible Power Supply) 54.

The Rubidium elution system of FIG. 2 may be used to assess variousaspects of the system, such as a concentration of ⁸²Rb, ⁸²Sr, or ⁸⁵Sr ina fluid that is eluted from the generator, the volume of the fluid thatis eluted from the generator, or the pressure of the fluid flowingthrough at least one portion of the system. Information about theseaspects of the system may be gathered by various elements of the system,and sent to the controller. The controller 28 and/or user interfacecomputer 44 (which may comprise a processor and memory) may analyze thisgathered data to assess the state of the system.

As shown in FIG. 2 , the pressure detector 62 is configured to detectthe in-line pressure of the bypass line, and to convey information aboutthis pressure to the controller. The pressure detector may be configuredto detect the in-line pressure elsewhere within the system, such as thefeed-line (saline supply-line).

The user interface computer 44 is depicted as being connected to aprinter 50, and having a USB port. The user interface of the userinterface computer 44 may be used to generate an output on the userinterface based on a result of the assessment. The printer 50 may beused to print out information about the state of the system, such as aactivity of ⁸²Rb, ⁸²Sr, or ⁸⁵Sr in a fluid that is eluted from thegenerator, the flow rate of the fluid that is eluted from the generator,or the pressure of the fluid flowing through at least one portion of thesystem. The USB port may be used to store an indication of the result ofthe assessment in a memory location, such as a flash drive.

The elution system of FIG. 2 may additionally have a dose calibrator 56that receives eluate via eluate line 41. The dose calibrator 56 may beused instead of a patient outlet, or in addition to a patient outlet,along with a valve that may be configured to direct fluid to the patientoutlet or to the dose calibrator. The dose calibrator 56 may comprise avial 58 (such as a 50 mL vial) that collects the fluid as it otherwiseexits the elution system. The dose calibrator 56 may be communicativelycoupled to the controller 28, and configured to send information to thecontroller 28, such as an activity concentration of ⁸²Rb, ⁸²Sr, or ⁸⁵Srin a fluid that is eluted from the generator. The dose calibrator 56 mayinclude a radioactivity shielding material.

In certain embodiments, the system is embodied in a portable (or mobile)cart that houses some or all of the generator, the processor, the pump,the memory, the patient line, the bypass line, the positron detector,and/or the calibrator. In an embodiment, the system may contain a“primary cart” and a “secondary cart”. Each cart can be mobile orstationary. As used herein, the term “primary cart” refers to the firstcart comprising components of the elution system such as a generator, aneluant reservoir, a pump, and/or a waste reservoir. The primary cartpreferably comprises a shielding assembly located within a primarycabinet. As used herein, the term “secondary cart” refers to the secondcart comprising other components such as a dose calibrator. Thesecondary cart preferably comprises a shielding assembly located withina second cabinet.

As used herein, the term “cabinet” refers to the outer structurestretching upward from platform surface of cart wherein the cabinetstructure house all the shielded and non-shielded components of thesystem. The cabinet structure may be made up of any of the radiationresistant material including but not limited to stainless steel,injection-molded polyurethane or any other suitable materials andcombinations thereof fitted together according to methods known to thoseskilled in the art. In an embodiment, the cabinet can be made of ashielding material.

As used herein, the term “quality control test” refers to the testsperformed on daily basis for evaluating the safety and efficacy ofelution system and more precisely the generator system. If any of thequality control tests fail, then the generator system is configured tonot perform a patient elution. Quality control measures may include, butare not limited to, checking and/or testing the status of each of thecolumns, breakthrough testing on at least one column, flow rate,leakage, column and tubing pressure, eluant volume, waste bottle volume,eluate reservoir volume, activity of parent and daughter isotopes,sensors, pump and valves functioning, checking the environmentsurrounding elution system, testing outputs produced by each of thecolumns, and/or performing testing on samples of theradiopharmaceuticals produced by columns, among other quality controlmeasures. Quality control system may be used to generate one or morequality reports relating to the quality of the radiopharmaceuticalsproduced by the elution system. Quality reports may include, but are notlimited to: analytical tests performed on the product; total yield ofthe products; failure reports for the product; failure reports for theone or more systems used to manufacture the product; and/or operatorerror reports, among other quality reports. Quality control system mayinterface with each individual system when performing the qualitycontrol tests.

In an embodiment, the radiopharmaceutical elution system comprises atleast a radioisotope generator, a patient line for infusing a patientwith a radioisotope eluate generated by the generator, an eluantreservoir, a pump for pumping eluant from the eluant reservoir to thegenerator, a controller for controlling the pump.

In an embodiment, the radiopharmaceutical elution system comprises asuitable eluant contained in an eluant reservoir, a radioactivegenerator containing a parent radioisotope that decays into acorresponding daughter radioisotope, a first tubing line interconnectingthe eluant reservoir and the generator, a pump for pumping the eluantfrom the eluant reservoir through said first tubing line, a first valvelocated on said tubing line and downstream the pump for directing theeluant to the generator or to a by-pass line, an eluate exiting thegenerator through a second tubing line and containing the daughterradioisotope, the second tubing line having a connection to receive theeluant from the by-pass line, a radioactivity detector on the secondtubing line downstream said connection, a second valve on the secondtubing line downstream the detector for directing the eluate to apatient line or to a waste line that is connected to a waste reservoir,the patient line is adapted for infusion into a patient, a controllerfor controlling the pump, the first valve and the second valve, and forreceiving the information from the detector, wherein the controller isconnected to an imaging software of a radioisotope imaging device thatis arranged for imaging the patient receiving the radioisotope infusionor a region of said patient.

In an embodiment of the invention, the controller preferably allows apatient infusion before establishment of said equilibrium; andpreferably once the generator recharge level is sufficient to provide adose required for a specific patient infusion. Generally, 90% of theregeneration is reached within 5 minutes and complete regeneration isreached after 10 minutes. Therefore, a patient elution can be possibleafter 4, 5, 6, 7 8 or 9 minutes, and preferably after 5 or 6 minutes.

In an embodiment of the invention, the radioisotope elution systemcomprises at least a radioisotope generator containing a parentradioisotope that decays into a daughter radioisotope, a patient linefor infusing a patient with a daughter radioisotope eluate generated bythe generator, a pump for pumping an eluant from an eluant reservoirinto the generator, and a controller for controlling the pump. In apreferred embodiment, the controller of the radioisotope elution systemis configured to calculate a real time amount of daughter radioisotopethat is available in the generator during the establishment of anequilibrium for decay of the parent radioisotope into its daughterradioisotope. Preferably, the controller provides real time informationat each instant during establishment of the equilibrium. This real timeinformation comprises at least the available amount of daughterradioisotope that can be infused to the patient. In an embodiment, thereal time information further comprises the flow rate of infusion thatis requested to infuse said available amount, and/or the duration ofinfusion that is requested to infuse said available amount. The user isenabled to select the desired dose, flow rate and duration of infusion.However, this embodiment of the elution system advantageously providesguidance the user to start a patient elution as soon as the desiredamount of daughter radioisotope is available, even when the generator isnot completely recharged (i.e. when the equilibrium of the decay of theparent radioisotope into the daughter radioisotope is not completelyattained or established). This feature is particularly useful in asituation when a stress agent was administered to the patient and theinfusion of daughter radioisotope was interrupted or delayed for anyreason, since the daughter radioisotope has to be infused to the patientbefore the end of the efficacy of the stress agent and this end ofefficacy may occur before establishment of the equilibrium. Therefore,the real time information on the available amount of daughterradioisotope allows the user to start a patient elution as soon as thedesired dose is available and prior to the end of efficacy of the stressagent. The end of efficacy of the stress agent usually depends on thenature of the stress agent, but may also be influenced by the dose ofstress agent that was administered to the patient and the patientcharacteristic in certain circumstances. In an embodiment, theradioisotope elution system further comprises a user interface, whichadvantageously displays the real time information provided by thecontroller. The available amount of daughter radioisotope can bedisplayed in terms of activity dose unit (mCi) or in terms of percentageof the desired dose to be eluted by the user. In an embodiment, thecontroller provides a notification to the user immediately once theavailable amount of daughter radioisotope reaches a needed amount (ordesired dose) that the user has previously entered into the system. Thisnotification can be audible or visual, or both.

In an embodiment, the controller of the radioisotope elution system isalso configured to calculate the time that remains for the equilibriumfor decay of the parent radioisotope into its daughter radioisotope isreached or established. This information about the time lapsed until theestablishment of the equilibrium is advantageously provided to the userby the controller.

In any of the embodiments disclosed herein, the daughter radioisotope ispreferably rubidium-82.

In another embodiment of the present invention, the following patientinfusion can be pre-programmed in the radioisotope elution system andthe controller advantageously starts a patient infusion corresponding tosaid pre-programmed patient infusion automatically when the availableamount of daughter radioisotope in the generator has reached asufficient amount for infusing the following pre-programmed patientinfusion. This feature advantageously allows the next patient infusionto start without any waste of time.

In another embodiment, the radioisotope elution system further comprisesa generator line by which the eluate exits the generator, and a tubingline system that directs the eluant from the eluant reservoir to thegenerator. Said tubing line system preferably comprises a first valvethat directs alternatively the eluant to the generator or a bypass line.The bypass line is preferably merged with a generator line at a mergingpoint. The system preferably further comprises a radioactivity detectordownstream the merging point for detecting the radioactivity of amixture of an eluate generated by the generator and the eluant directedby the bypass line. The controller of the system preferably controls thefirst valve and the pump for adjusting: i) the radioactivity per volumeat the merging point, or ii) a flow rate of the mixture at the mergingpoint, or iii) both. Preferably, the radioactivity per volume and/or theflow rate is determined in accordance with the patient requirement. Thispatient requirement is preferably based on at least one characteristicof the patient, such as age, sex, body weight, body mass index, bodycircumference and/or a surface area. This patient requirement may alsobe based on the organ or the part of the patient that is intended forimaging. Said organ or part of the patient can be the heart, the brain,the kidneys, a limb or the blood vessels; when the daughter radioisotopeis rubidium-82.

In another embodiment, the radioisotope elution system further comprisesa radioisotope imaging device for imaging the patient or an organ or apart of the patient, and the controller is connected to an imagingsoftware of the radioisotope imaging device. In an aspect of thisembodiment, the controller is preferably preconfigured to start an imageacquisition at a predetermined time after the patient infusion has begunor has ended.

In another embodiment, the radioisotope elution system further comprisesa tubing system 37 interconnecting the radioisotope elution system witha stress agent reservoir 39. In an aspect of this embodiment, thecontroller 28 is preferably configured to control the infusion of astress agent contained in the stress agent reservoir to the patient. Thestress agent infusion is preferably performed at a predetermined timeprior to infusing the daughter radioisotope eluate to the patient. Inanother preferred aspect of this embodiment, the stress agent infusionis automated and the controller 28 controls the dose of stress agent andthe pre-determined time prior to infusing a patient with a daughterradioisotope eluate. The dose of stress agent can be determined inaccordance with the patient requirement. Said patient requirement isbased on at least one characteristic of the patient, such as age, sex,body weight, body mass index, body circumference and/or a surface area.Said patient requirement may also be based on the organ or the part ofthe patient that is intended for imaging. The organ or part of thepatient is preferably the heart, the brain, the kidneys, a limb or theblood vessels, when the daughter radioisotope is rubidium-82.

In a further embodiment of the present invention, the controller of theradioisotope elution system is advantageously configured to calculate anamount of daughter radioisotope that is available in the generator for apatient infusion and estimate the amount of daughter radioisotope thatwill be available in the generator the following days. The controller ispreferably configured to receive information from the user about thepatient infusions that are intended to be performed in the nextfollowing days or weeks. The controller is advantageously configured todisplay on the interface a recommended day for infusing each of thepatient infusions that are intended. Said recommended day is suggestedby the controller in accordance with the amount of daughter radioisotopethat is available in the generator on each day, so as to perform amaximal number of patient infusions. According to this embodiment, thecontroller will advantageously prioritize the patient infusions thatrequire the larger amounts of daughter radioisotope during the beginningof the generator's life (when the available amount in the generator ishigher) and recommend the patient infusions that require the smalleramounts of daughter radioisotope towards the end of the generator's life(when the available amount in the generator is lower). This feature ofthe system advantageous supports the user with the schedule of patientso as to maximize the performance of the system and the schedule.

In an embodiment of the present invention, the controller is configuredto display a plan for optimizing the number of patients that will beinfused during the same day, during the week, during the month or duringthe entire life of the generator. In an embodiment, the generator lifeis about 60 days. The plan preferably proposes a specific order forinfusing the patients. The plan displayed by the controller, is specificfor a particular day and is based on at least one of the followingparameters: the quality control result, the time for establishment ofthe equilibrium in the generator, at least one parameter orcharacteristic of the patients intended for infusion on that particularday. Preferably, the parameter or characteristic of the patients thatare intended for infusion on that particular day are communicated to thecontroller in the morning or one of the previous day. Different meanscan be used for communicating the information to the controllerincluding entering the information on the user interface.

In an embodiment of the invention, the elution system further comprisesa software component for predicting the recharge percentage of thegenerator and allow a patient infusion before complete recharge of thegenerator. Full recharge means that the equilibrium is reached.

In an embodiment of the invention, the elution system further comprisesa valve for introducing a stress agent into the patient line and anadditional pump for pumping the stress agent into the patient line.Advantageously, the pump and the valve are communicatively coupled tothe controller which controls the amount of stress agent that isadministered to the patient, and the time prior to the following patientelution. The controller is preferably automated to perform thecalculation of the amount of stress agent that should be delivered to apatient, to deliver the stress agent to the patient, and to start thefollowing patient elution at the optimistic time after the stress agentinfusion. In an embodiment of the invention, the stress agent isdipyridamole, adenosine, adenosine triphosphate, regadenason, ordobutamine. In a preferred embodiment, the stress agent is regadenason.In another embodiment, the stress agent is administered to the patientseparately, i.e. without using the elution system. Stress agent can beadministered depending upon the patient parameters like age, sex, bodyweight, body mass index, body circumference and/or surface area. Inalternate embodiments, the controller is configured to automaticallycalculate and infuse the stress agent dose depending upon patientcharacteristics at a time ranging from 5-15 minutes after rest doseadministration of radiopharmaceutical.

In an embodiment of the invention, the elution system further comprisesa stress agent source. In an embodiment, the stress agent infusion isperformed at a predetermined time prior to infusing the daughterradioisotope eluate to the patient. In an embodiment, saidpre-determined time is dependent on the nature of the stress agent.

In an embodiment of the invention, the total dose of infusedradioisotope to a patient, the activity per volume, and the flow rate ofthe eluate are adjusted for each patient in accordance with at least onepatient characteristic, such as age, sex, body weight, body mass index,body circumference or the surface area. In an embodiment, the surfacearea is the surface area of the region that is intended for imaging. Inanother embodiment, the surface area is the total surface area of apatient. Preferably, the pump is communicatively coupled to thecontroller to drive the eluate containing the radioisotope at a lowerflow rate for infusing in a pediatric patient or a geriatric patient. Apediatric patient is a child. Preferably, a pediatric patient has below21, or below 18 years old, or below 14 years old, or below 11 years old,or any interval between 1 day and 21 years old. A geriatric patient hasabove 65 years old, above 70 years old, or above 75 years old.

In an embodiment of the present invention, the pump pushes the eluantthrough bypass line at a certain flow rate for moving the radioactivityto the target organ of the patient rapidly after completion of elutionthrough generator. Said flow rate is preferably higher than the flowrate for infusing the eluate containing the radioisotope, and ispreferably between 10 mL/min and 100 mL/min.

In an embodiment of the invention, the controller automaticallycalculates the dose (total amount of radioactivity) to be infused to thepatient, based on the age, sex, body weight, body mass index, bodycircumference and/or the surface area.

In an embodiment of the present invention, the patient is connected to aradioisotope imaging device that is arranged for imaging the patient ora region of the patient; and the elution system is connected to animaging software of the imaging device such that the software starts theimage acquisition at the pre-calculated time point. The time point ispreferably 1 minute, 1.5 minute, 2 minutes, 2.5 minutes, or 3 minutesafter the patient infusion has started.

In an embodiment of the invention, the daughter radioisotope isrubidium-82 (⁸²Rb) and the controller is connected to a softwarecomponent that provides graphical output of the ⁸²Rb activity detectedby the detector at any time and pin particular during a patient elution.The software may display an alert if there is any deviation fromstandard activity and/or rescanning (or reimaging) the patient isrequired for better imaging and diagnosis.

While this invention has been described in detail with reference tocertain preferred embodiments, it should be appreciated that the presentinvention is not limited to those precise embodiments. Rather, in viewof the present disclosure, which describes the current best mode forpracticing the invention, many modifications and variations wouldpresent themselves to those skilled in the art without departing fromthe scope, and spirit of this invention. Any combination of theembodiments described herein are specifically intended to be covered bythe present inventors.

What is claimed:
 1. A radioisotope elution system comprising aradioisotope generator containing a parent radioisotope that decays intoa daughter radioisotope, a patient line for infusing a patient with adaughter radioisotope eluate generated by the generator, a pump forpumping an eluant from an eluant reservoir into the generator, and acontroller for controlling the pump; wherein the system is characterizedin that: the controller is configured to calculate a real time amount ofdaughter radioisotope that is available in the generator from the startof an establishment of an equilibrium for decay of the parentradioisotope into its daughter radioisotope; and the controller isconfigured to provide real time information before the establishment ofthe equilibrium, said real time information comprising the availableamount of eluted daughter radioisotope that can be infused to thepatient from the start of the establishment of the equilibrium for decayof the parent radioisotope into the daughter radioisotope; wherein thepatient infusion is pre-programmed and the controller is configured tostart a patient infusion corresponding to said pre-programmed patientinfusion automatically when the available amount of a daughterradioisotope in the generator has reached a required amount forinfusion.
 2. The radioisotope elution system of claim 1, wherein thereal time information further comprises the flow rate of infusion thatis requested to infuse said available amount.
 3. The radioisotopeelution system of claim 1, wherein the system further comprises a userinterface, wherein the controller displays the real time information onthe interface.
 4. The radioisotope elution system of claim 1, whereinthe available amount of daughter radioisotope is displayed in terms ofactivity dose unit.
 5. The radioisotope elution system of claim 1,wherein the controller is further configured to calculate the timelapsed until the establishment of an equilibrium for decay of the parentradioisotope into its daughter radioisotope.
 6. The radioisotope elutionsystem of claim 1, wherein the controller provides the information aboutthe time lapsed until the establishment of the equilibrium.
 7. Theradioisotope elution system of claim 1, wherein the controller notifiesthe user of the system immediately once the available amount of daughterradioisotope reaches a needed amount that the user has entered into thesystem.
 8. The radioisotope elution system of claim 7, wherein thenotification is audible, visual or both.
 9. The radioisotope elutionsystem of claim 1, wherein the daughter radioisotope is rubidium-82. 10.The radioisotope elution system of claim 1, wherein the system furthercomprises a radioisotope imaging device for imaging the patient or anorgan or a part of the patient; wherein the controller is connected toan imaging software of the radioisotope imaging device.
 11. Theradioisotope elution system of claim 10, wherein the controller isconfigured to start an image acquisition at a predetermined time afterthe patient infusion has begun or has ended.
 12. The radioisotopeelution system of claim 1, wherein the system further comprises a tubingsystem interconnecting the radioisotope elution system with a stressagent reservoir, wherein the controller is configured to control theinfusion of a stress agent contained in the stress agent reservoir tothe patient.
 13. The radioisotope elution system of claim 12, whereinthe stress agent infusion is performed at a predetermined time prior toinfusing the daughter radioisotope eluate to the patient.
 14. Theradioisotope elution system of claim 12, wherein the stress agentinfusion is automated and the controller controls the dose of stressagent and the pre-determined time prior to infusing a patient with adaughter radioisotope eluate.
 15. The radioisotope elution system ofclaim 1, wherein the pump and the valve are communicatively coupled tothe controller to control the amount of stress agent that isadministered to the patient.
 16. A radioisotope elution systemcomprising; a radioisotope generator containing a parent radioisotopethat decays into a daughter radioisotope; a patient line for infusing apatient with a daughter radioisotope eluate generated by the generator;a pump for pumping an eluant from an eluant reservoir into thegenerator; a controller for controlling the pump; a generator line bywhich the eluate exits the generator; a tubing line system that directsthe eluant from the eluant reservoir to the generator; wherein thetubing line system comprises a first valve that directs alternativelythe eluant to the generator or a bypass line; wherein the bypass line ismerged with a generator line at a merging point; wherein the systemfurther comprises a radioactivity detector downstream the merging pointfor detecting the radioactivity of a mixture of an eluate generated bythe generator and the eluant directed by the bypass line; wherein thecontroller controls the first valve and the pump for adjusting: theradioactivity per volume at the merging point, or a flow rate of themixture at the merging point, or both; wherein the system ischaracterized in that: the controller is configured to calculate a realtime amount of daughter radioisotope that is available in the generatorfrom the start of an establishment of an equilibrium for decay of theparent radioisotope into its daughter radioisotope; and the controlleris configured to provide real time information before the establishmentof the equilibrium, said real time information comprising the availableamount of eluted daughter radioisotope that can be infused to thepatient from the start of the establishment of the equilibrium for decayof the parent radioisotope into the daughter radioisotope; wherein thepatient infusion is pre-programmed and the controller is configured tostart a patient infusion corresponding to said pre-programmed patientinfusion automatically when the available amount of a daughterradioisotope in the generator has reached a required amount forinfusion.
 17. The radioisotope elution system of claim 16, wherein theradioactivity per volume or the flow rate is determined in accordancewith the patient requirement.
 18. The radioisotope elution system ofclaim 17, wherein the patient requirement is based on at least onecharacteristic of the patient, said at least one characteristic of thepatient is age, sex, body weight, body mass index, body circumference orsurface area.
 19. The radioisotope elution system of claim 17, whereinthe patient requirement is based on the organ or the part of the patientthat is intended for imaging.
 20. The radioisotope elution system ofclaim 19, wherein the organ or the part of the patient is heart, brain,kidney, limb or blood vessel; and wherein the daughter radioisotope isrubidium-82.